US8133995B2ExpiredUtilityPatentIndex 51
Substituted 4-amino-pyrrolotriazine derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
Est. expiryDec 2, 2025(expired)· nominal 20-yr term from priority
Inventors:DIXON JULIEMAGNUSON STEVENPHILLIPS BARTONWANG YAMINLI TANDYPARCELLA KYLENEWCOM JASONKLUENDER HAROLDHONG ZHENQIUCHANDLER BRENTZHANG ZHONGHUAALLEGUE KRISTENLIU ZHENG
A61P 9/00A61P 35/00A61P 35/04C07D 487/04A61K 31/53
51
PatentIndex Score
4
Cited by
33
References
13
Claims
Abstract
This invention relates to novel pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and the use of those compounds and compositions for the prevention and/or treatment of hyper-proliferative disorders and diseases associated with angiogenesis.
Claims
exact text as granted — not AI-modifiedThe invention claimed is:
1. A compound of formula (I)
wherein
R 1 represents
1.1) phenyl or a bicyclic carbocycle of 9-10 ring members, in which at least one ring is aromatic, R 1 optionally bearing up to 4 substituents independently selected from the group consisting of
1.1.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.1.a1) halogen;
1.1.a2) OR 5 wherein R 5 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino;
1.1.a3) —NR 6 R 7 in which R 6 and R 7 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 7a wherein R 7a represents H or (C 1 -C 3 )alkyl, or R 6 and R 7 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 8 wherein R 8 represents H or (C 1 -C 3 )alkyl; and
1.1.a4) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
1.1.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.1.b1) halogen; and
1.1.b2) OR 9 wherein R 9 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or (C 1 -C 3 )mono- or di-alkylamino;
1.1.c) OR 10 wherein
R 10 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.1.c1) halogen;
1.1.c2) OR 11 wherein R 11 represents H or (C 1 -C 3 )alkyl which may optionally bear (C 1 -C 3 )mono- or di-alkylamino; and
1.1.c3) NR 12 R 13 in which R 12 and R 13 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 12 and R 13 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 14 wherein R 14 represents H or (C 1 -C 3 )alkyl;
1.1.d) —C(O)—OR 15 wherein R 15 represents H or —(C 1 -C 4 )alkyl which may optionally bear up to 3 halogens;
1.1.e) —C(O)—NR 16 R 17 wherein
R 16 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 17 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.1.e1) halogen;
1.1.e2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
1.1.e3) phenyl;
1.1.e4) —SO 2 CH 3 ;
1.1.e5) —OR 18 wherein R 18 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.e6) —NR 19 R 20 in which R 19 and R 20 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 19 and R 20 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 21 wherein R 21 represents H or (C 1 -C 3 )alkyl;
1.1.f) —N(R 22 )—C(O)—R 23 wherein
R 22 represents H or (C 1 -C 3 )alkyl; and
R 23 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.1.f1) optionally substituted phenyl,
1.1.f2) OR 24 wherein R 24 represents H or (C 1 -C 3 )alkyl, or
1.1.f3) NR 25 R 26 wherein R 25 and R 26 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 25 and R 26 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 27 wherein R 27 represents H or (C 1 -C 3 )alkyl;
1.1.g) —SO 2 NR 28 R 29 wherein
R 28 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 29 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with:
1.1.g1) halogen;
1.1.g2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
1.1.g3) phenyl;
1.1.g4) —SO 2 CH 3 ;
1.1.g5) —OR 30 wherein R 30 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.g6) —NR 31 R 32 in which R 31 and R 32 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 31 and R 32 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 33 wherein R 33 represents H or (C 1 -C 3 )alkyl;
1.1.h) —N(R 34 )—SO 2 —R 35 wherein
R 34 represents H or (C 1 -C 3 )alkyl, and
R 35 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.1.h1) halogen;
1.1.h2) optionally substituted phenyl,
1.1.h3) OR 36 wherein R 36 represents H or (C 1 -C 3 )alkyl, or
1.1.h4) NR 37 R 38 wherein R 37 and R 38 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 37 and R 38 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 39 wherein R 39 represents H or (C 1 -C 3 )alkyl;
1.1.i) —NR 40 R 41 in which R 40 and R 41 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 42 in which R 42 represents H or (C 1 -C 3 )alkyl, or R 40 and R 41 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 43 wherein R 43 represents H or (C 1 -C 3 )alkyl;
1.1.j) halogen;
1.1.k) optionally substituted phenyl;
1.1.l) NO 2 ;
1.1.m) CN; and
1.1.n) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
or
R 1 represents
1.2) a 5-6 membered aromatic heterocycle containing up to 3 heteroatoms independently selected from the group consisting of N, O, and S; or a bicyclic heterocycle of 8-10 ring members in which at least one ring is aromatic and contains up to 3 moieties independently selected from the group consisting of N, N→O, O, and S, and any non-aromatic ring of said bicyclic heterocycle optionally contains up to three moieties independently selected from the group consisting of O, S, S(O), S(O) 2 , and NR 44 wherein R 44 represents H or —(C 1 -C 3 )alkyl; said R 1 heterocycle optionally bearing up to 4 substituents independently selected from the group consisting of
1.2.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.2.a1) halogen;
1.2.a2) OR 45 wherein R 45 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino;
1.2.a3) —NR 46 R 47 in which R 46 and R 47 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 47a wherein R 47a represents H or (C 1 -C 3 )alkyl, or R 46 and R 47 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 48 wherein R 48 represents H or (C 1 -C 3 )alkyl; and
1.2.a4) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
1.2.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.2.b1) halogen; and
1.2.b2) OR 49 wherein R 49 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino;
1.2.c) OR 50 wherein
R 50 represents H; phenyl; benzyl; —(C 3 -C 6 )cycloalkyl; or —(C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.2.c1) halogen;
1.2.c2) OR 51 wherein R 51 represents H or (C 1 -C 3 )alkyl which may optionally bear —(C 1 -C 3 )mono- or di-alkylamino; and
1.2.c3) —NR 52 R 53 in which R 52 and R 53 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 52 and R 53 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 54 wherein R 54 represents H or (C 1 -C 3 )alkyl;
1.2.d) —C(O)—OR 55 wherein R 55 represents H or —(C 1 -C 4 )alkyl which may optionally bear up to 3 halogens;
1.2.e) —C(O)—NR 56 R 57 wherein
R 56 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 57 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.e1) halogen;
1.2.e2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
1.2.e3) phenyl;
1.2.e4) —SO 2 CH 3 ;
1.2.e5) —OR 58 wherein R 58 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.2.e6) —NR 59 R 60 in which R 59 and R 60 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 59 and R 60 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 61 wherein R 61 represents H or (C 1 -C 3 )alkyl;
1.2.f) —N(R 62 )—C(O)—R 63 wherein
R 62 represents H or (C 1 -C 3 )alkyl; and
R 63 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.2.f1) optionally substituted phenyl,
1.2.f2) OR 64 wherein R 64 represents H or (C 1 -C 3 )alkyl, or
1.2.f3) NR 65 R 66 wherein R 65 and R 66 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 65 and R 66 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 67 wherein R 67 represents H or (C 1 -C 3 )alkyl;
1.2.g) —SO 2 NR 68 R 69 wherein
R 68 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 69 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.g1) halogen;
1.2.g2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
1.2.g3) phenyl;
1.2.g4) —SO 2 CH 3 ;
1.2.g5) —OR 70 wherein R 70 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.2.g6 —NR 71 R 72 in which R 71 and R 72 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 71 and R 72 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 73 wherein R 73 represents H or (C 1 -C 3 )alkyl;
1.2.h) —N(R 74 )—SO 2 —R 75 wherein
R 74 represents H or (C 1 -C 3 )alkyl, and
R 75 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.2.h1) halogen;
1.2.h2) optionally substituted phenyl,
1.2.h3) OR 76 wherein R 76 represents H or (C 1 -C 3 )alkyl, or
1.2.h4) NR 77 R 78 wherein R 77 and R 78 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 77 and R 78 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 79 wherein R 79 represents H or (C 1 -C 3 )alkyl;
1.2.i) —NR 80 R 81 in which R 80 and R 81 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 81a wherein R 81a represents H or (C 1 -C 3 )alkyl, or R 80 and R 81 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 82 wherein R 82 represents H or (C 1 -C 3 )alkyl;
1.2.j) halogen;
1.2.k) optionally substituted phenyl;
1.2.l) NO 2 ;
1.2.m) CN; and
1.2.n) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
R 2 represents hydrogen; halogen; —(C 1 -C 5 )alkyl which may optionally bear halogen; or —O(C 1 -C 3 )alkyl which may optionally bear halogen;
R 3 represents
3.1) —(C 1 -C 5 )alkyl which is substituted with
3.1.a) -halogen;
3.1.b) phenyl optionally substituted with halogen, —(C 1 -C 3 )alkyl, or —(C 1 -C 3 )alkoxy,
3.1.c) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N, optionally substituted with halogen or —(C 1 -C 3 )alkyl,
3.1.d) —CN,
3.1.e) —OR 83 wherein R 83 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
3.1.e1) halogen;
3.1.e2) optionally substituted phenyl;
3.1.e3) —S(O) 2 CH 3 ;
3.1.e4) OR 84 wherein R 84 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino; and
3.1.e5) —NR 85 R 86 in which R 85 and R 86 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 85 and R 86 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 87 wherein R 87 represents H or (C 1 -C 3 )alkyl;
3.1.f) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen or OR 88 wherein R 88 represents H or (C 1 -C 3 )alkyl; or
3.1.g) —NR 89 R 90 wherein
R 89 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 90 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
3.1.g1) halogen;
3.1.g2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.1.g3) phenyl;
3.1.g4) —SO 2 CH 3 ;
3.1.g5) —OR 91 wherein R 91 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
3.1.g6) —NR 92 R 93 in which R 92 and R 93 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 92 and R 93 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 94 wherein R 94 represents H or (C 1 -C 3 )alkyl; or
3.1.g7) R 89 and R 90 may be joined and taken together with the N to which they are attached form an aromatic or nonaromatic 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 95 wherein R 95 represents H or (C 1 -C 3 )alkyl;
3.2)
wherein
R 96 represents
3.2.a) H,
3.2.b) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen or —(C 1 -C 3 )alkoxy; or
3.2.c) —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.2.c1) halogen;
3.2.c2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.2.c3) phenyl;
3.2.c4) —S(O) 2 CH 3 ;
3.2.c5) —OR 97 wherein R 97 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino; and
3.2.c6) —NR 98 R 99 in which R 98 and R 99 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 99a wherein R 99a represents H or (C 1 -C 3 )alkyl, or R 98 and R 99 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 100 wherein R 100 represents H or (C 1 -C 3 )alkyl;
3.3)
wherein R 101 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.3.a) halogen; and
3.3.b) phenyl;
3.4)
wherein
R 102 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 103 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.4.a) halogen;
3.4.b) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.4.c) phenyl;
3.4.d) —S(O) 2 CH 3 ;
3.4.e) OR 104 wherein R 104 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
3.4.f) —NR 105 R 106 in which R 105 and R 106 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 105 and R 106 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 107 wherein R 107 represents H or (C 1 -C 3 )alkyl;
3.5) optionally substituted phenyl;
3.6) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.7) halogen;
3.8) —CN; or
3.9) —CH═N—OR 108 wherein R 108 represents H or —C(O)—(C 1 -C 3 )alkyl;
R 4 represents
4.1) —(C 1 -C 5 )alkyl which is substituted with
4.1.a) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen or OR 109 wherein R 109 represents H or (C 1 -C 3 )alkyl;
4.1.b) -halogen;
4.1.c) —OR 110 wherein R 110 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.c1) halogen;
4.1.c2) phenyl;
4.1.c3) —S(O) 2 CH 3 ;
4.1.c4) OR 111 wherein R 111 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.c5) —NR 112 R 113 in which R 112 and R 113 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 112 and R 113 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 114 wherein R 114 represents H or (C 1 -C 3 )alkyl;
4.1.d) —NR 115 R 116 wherein
R 115 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen and
R 116 represents H, optionally substituted phenyl, or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.d1) halogen;
4.1.d2) —S(O) 2 CH 3 ;
4.1.d3) OR 117 wherein R 117 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.d4) —NR 118 R 119 in which R 118 and R 119 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 118 and R 119 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 120 wherein R 120 represents H or (C 1 -C 3 )alkyl;
4.1.e) optionally substituted phenyl; or
4.1.f) a 5-6 membered aromatic heterocycle containing up to two heteroatoms selected from O, S, and N;
4.2)
wherein R 121 represents —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 122 in which R 122 represents H or —(C 1 -C 3 )alkyl;
d represents 1, 2, or 3;
e represents 0 or 1;
f represents 0, 1, or 2;
4.3)
wherein R 123 represents —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 124 in which R 124 represents H or —(C 1 -C 3 )alkyl;
g represents 1, 2, or 3;
h represents 0, 1, or 2;
4.4)
wherein
R 125 represents
4.4.a) H;
4.4.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 126 in which R 126 represents H or —(C 1 -C 3 )alkyl which in turn is optionally substituted with halogen;
4.4.c) —SO 2 R 127 wherein R 127 represents optionally substituted phenyl, or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 128 wherein R 128 represents H or (C 1 -C 3 )alkyl;
4.4.d) —C(O)R 129 wherein
R 129 represents
4.4.d1) optionally substituted phenyl,
4.4.d2) —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.4.d2.1) halogen;
4.4.d2.2) optionally substituted phenyl;
4.4.d2.3) —S(O) 2 CH 3 ;
4.4.d2.4) —OR 130 wherein R 130 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.4.d2.5) —NR 131 R 132 in which R 131 and R 132 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 131 and R 132 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 133 wherein R 133 represents H or (C 1 -C 3 )alkyl;
4.4.d3) —OR 134 wherein R 134 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.4.d4) NR 135 R 136 wherein R 135 and R 136 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 135 and R 136 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 137 wherein R 137 represents H or (C 1 -C 3 )alkyl; and
j represents 1, 2, or 3;
4.5)
wherein
X represents C or N;
R 138 represents
4.5.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
4.5.a1) halogen;
4.5.a2) OR 139 wherein R 139 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino;
4.5.a3) —NR 140 R 141 in which R 140 and R 141 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 141a wherein R 141a represents H or (C 1 -C 3 )alkyl, or R 140 and R 141 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 142 wherein R 142 represents H or (C 1 -C 3 )alkyl; and
4.5.a4) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
4.5.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
4.5.b1) halogen; and
4.5.b2) OR 143 wherein R 143 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.5.c) OR 144 wherein
R 144 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
4.5.c1) halogen;
4.5.c2) OR 145 wherein R 145 represents H or (C 1 -C 3 )alkyl which may optionally bear (C 1 -C 3 )mono- or di-alkylamino; and
4.5.c3) NR 146 R 147 in which R 146 and R 1473 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 146 and R 147 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 148 wherein R 148 represents H or (C 1 -C 3 )alkyl;
4.5.d) —C(O)—OR 149 wherein R 149 represents H or —(C 1 -C 4 )alkyl which may optionally bear up to 3 halogens;
4.5.e) —C(O)—NR 150 R 151 wherein
R 150 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 151 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.e1) halogen;
4.5.e2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
4.5.e3) phenyl;
4.5.e4) —SO 2 CH 3 ;
4.5.e5) —OR 152 wherein R 152 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.5.e6) —NR 153 R 154 in which R 153 and R 154 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 153 and R 154 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 155 wherein R 155 represents H or (C 1 -C 3 )alkyl;
4.5.f) —N(R 156 )—C(O)—R 157 wherein
R 156 represents H or (C 1 -C 3 )alkyl; and
R 157 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
4.5.f1) optionally substituted phenyl,
4.5.f2) OR 158 wherein R 158 represents H or (C 1 -C 3 )alkyl, or
4.5.f3) NR 159 R 160 wherein R 159 and R 160 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 159 and R 160 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 161 wherein R 161 represents H or (C 1 -C 3 )alkyl;
4.5.g) —SO 2 NR 162 R 163 wherein
R 162 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 163 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.g1) halogen;
4.5.g2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
4.5.g3) phenyl;
4.5.g4) —SO 2 CH 3 ;
4.5.g5) —OR 164 wherein R 164 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.5.g6) —NR 165 R 166 in which R 165 and R 166 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 165 and R 166 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 167 wherein R 167 represents H or (C 1 -C 3 )alkyl;
4.5.h) —N(R 168 )—SO 2 —R 169 wherein
R 168 represents H or (C 1 -C 3 )alkyl, and
R 169 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
4.5.h1) halogen,
4.5.h2) optionally substituted phenyl,
4.5.h3) OR 170 wherein R 170 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen, or
4.5.h4) NR 171 R 172 wherein R 171 and R 172 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 171 and R 172 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 173 wherein R 173 represents H or (C 1 -C 3 )alkyl;
4.5.i) —NR 174 R 175 in which R 174 and R 175 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 175a wherein R 175a represents H or (C 1 -C 3 )alkyl, or R 174 and R 175 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 176 wherein R 176 represents H or (C 1 -C 3 )alkyl;
4.5.j) halogen;
4.5.k) optionally substituted phenyl;
4.5.l) NO 2 ;
4.5.m) CN; or
4.5.n) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N; and
k represents 0, 1, or 2;
4.6)
wherein R 177 represents H or —(C 1 -C 3 )alkyl; and
m represents 1, 2, or 3;
4.7)
n represents 1, 2, or 3; and
p represents 0, 1, or 2;
4.8)
wherein
q represents 1, 2, or 3;
4.9)
wherein
R 178 represents
4.9.a) H;
4.9.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 179 in which R 179 represents H or (C 1 -C 3 )alkyl optionally substituted with halogen;
4.9.c) —SO 2 R 180 wherein R 180 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl, which may be substituted with halogen or —OR 181 wherein R 181 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.9.d) —C(O)R 182 wherein R 182 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.9.d1) halogen;
4.9.d2) optionally substituted phenyl;
4.9.d3) —S(O) 2 CH 3 ;
4.9.d4) OR 183 wherein R 183 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.9.d5) —NR 184 R 185 in which R 184 and R 185 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 185a wherein R 185a represents H or (C 1 -C 3 )alkyl, or R 184 and R 185 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 186 wherein R 186 represents H or (C 1 -C 3 )alkyl;
4.9e) —C(O)OR 187 wherein R 187 represents (C 1 -C 3 )alkyl; or
4.9.f) —C(O)—NR 188 R 189 wherein R 188 and R 189 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 188 and R 189 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 190 wherein R 190 represents H or (C 1 -C 3 )alkyl;
r represents 0, 1, or 2; and
s represents 0 or 1;
4.10)
wherein
R 191 represents
4.10.a) H;
4.10.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 192 in which R 192 represents H or (C 1 -C 3 )alkyl;
4.10c) —SO 2 R 193 wherein R 193 represents phenyl or —(C 1 -C 3 )alkyl, both of which may be substituted with halogen or —(C 1 -C 3 )alkyl;
4.10.d) —C(O)R 194 wherein R 194 represents (C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.10.d1) halogen;
4.10.d2) phenyl;
4.10.d3) —S(O) 2 CH 3 ;
4.10.d4) OR 195 wherein R 195 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.10.d5) —NR 196 R 197 in which R 196 and R 197 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 197a wherein R 197a represents H or (C 1 -C 3 )alkyl, or R 196 and R 197 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 198 wherein R 198 represents H or (C 1 -C 3 )alkyl;
4.10.e) —C(O)OR 199 wherein R 199 represents (C 1 -C 3 )alkyl; or
4.10.f) —C(O)—NR 200 R 201 wherein R 200 and R 201 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 200 and R 201 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 202 wherein R 202 represents H or (C 1 -C 3 )alkyl; and
X represents O, S, S(O), S(O) 2 , or NR 203 wherein
R 203 represents H or —(C 1 -C 3 )alkyl; and
t represents 0, 1, or 2;
4.11) halogen; or
4.12) CN;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 wherein in formula (I)
R 1 represents
1.1) phenyl which may optionally bear up to 4 substituents independently selected from the group consisting of
1.1.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.1.a1) halogen;
1.1.a2) OR 5 wherein R 5 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino;
1.1.a3) —NR 6 R 7 in which R 6 and R 7 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 7a wherein R 7a represents H or (C 1 -C 3 )alkyl, or R 6 and R 7 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 8 wherein R 8 represents H or (C 1 -C 3 )alkyl; and
1.1.a4) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
1.1.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.1.b1) halogen;
1.1.c) OR 10 wherein
R 10 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.1.c1) halogen;
1.1.c2) OR 11 wherein R 11 represents H or (C 1 -C 3 )alkyl which may optionally bear (C 1 -C 3 )mono- or di-alkylamino; and
1.1.c3) NR 12 R 13 in which R 12 and R 13 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 12 and R 13 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 14 wherein R 14 represents H or (C 1 -C 3 )alkyl;
1.1.e) —C(O)—NR 16 R 17 wherein
R 16 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 17 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.1.e1) halogen;
1.1.e3) phenyl;
1.1.e4) —SO 2 CH 3 ;
1.1.e5) —OR 18 wherein R 18 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.e6) —NR 19 R 20 in which R 19 and R 20 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 19 and R 20 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 21 wherein R 21 represents H or (C 1 -C 3 )alkyl;
1.1.f) —N(R 22 )—C(O)—R 23 wherein
R 22 represents H or (C 1 -C 3 )alkyl; and
R 23 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.1.f1) optionally substituted phenyl,
1.1.f2) OR 24 wherein R 24 represents H or (C 1 -C 3 )alkyl, or
1.1.f3) NR 25 R 26 wherein R 25 and R 26 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 25 and R 26 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 27 wherein R 27 represents H or (C 1 -C 3 )alkyl;
1.1.g) —SO 2 NR 28 R 29 wherein
R 28 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 29 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with:
1.1.g1) halogen;
1.1.g3) phenyl;
1.1.g4) —SO 2 CH 3 ;
1.1.g5) —OR 30 wherein R 30 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.g6) —NR 31 R 32 in which R 31 and R 32 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 31 and R 32 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 33 wherein R 33 represents H or (C 1 -C 3 )alkyl;
1.1.h) —N(R 34 )—SO 2 —R 35 wherein
R 34 represents H or (C 1 -C 3 )alkyl, and
R 35 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.1.h1) halogen;
1.1.h2) optionally substituted phenyl,
1.1.h3) OR 36 wherein R 36 represents H or (C 1 -C 3 )alkyl, or
1.1.h4) NR 37 R 38 wherein R 37 and R 38 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 37 and R 38 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 39 wherein R 39 represents H or (C 1 -C 3 )alkyl;
1.1.i) —NR 40 R 41 in which R 40 and R 41 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 42 in which R 42 represents H or (C 1 -C 3 )alkyl, or R 40 and R 41 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 43 wherein R 43 represents H or (C 1 -C 3 )alkyl;
1.1.j) halogen;
1.1.l) NO 2 ;
1.1.m) CN; and
1.1.n) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
or
R 1 represents
1.2) a 5-6 membered aromatic heterocycle containing up to 3 heteroatoms independently selected from the group consisting of N, O, and S; said R 1 heterocycle optionally bearing up to 4 substituents independently selected from the group consisting of
1.2.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.2.a1) halogen;
1.2.a2) OR 45 wherein R 45 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino;
1.2.a3) —NR 46 R 47 in which R 46 and R 47 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 47a wherein R 47a represents H or (C 1 -C 3 )alkyl, or R 46 and R 47 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 48 wherein R 48 represents H or (C 1 -C 3 )alkyl; and
1.2.a4) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
1.2.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.2.b1) halogen;
1.2.c) OR 50 wherein
R 50 represents H; phenyl; benzyl; —(C 3 -C 6 )cycloalkyl; or —(C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.2.c1) halogen;
1.2.c2) OR 51 wherein R 51 represents H or (C 1 -C 3 )alkyl which may optionally bear —(C 1 -C 3 )mono- or di-alkylamino; and
1.2.c3) —NR 52 R 53 in which R 52 and R 53 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 52 and R 53 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 54 wherein R 54 represents H or (C 1 -C 3 )alkyl;
1.2.e) —C(O)—NR 56 R 57 wherein
R 56 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 57 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.e1) halogen;
1.2.e3) phenyl;
1.2.e4) —SO 2 CH 3 ;
1.2.e5) —OR 58 wherein R 58 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.2.e6) —NR 59 R 60 in which R 59 and R 60 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 59 and R 60 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 61 wherein R 61 represents H or (C 1 -C 3 )alkyl;
1.2.f) —N(R 62 )—C(O)—R 63 wherein
R 62 represents H or (C 1 -C 3 )alkyl; and
R 63 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.2.f1) optionally substituted phenyl,
1.2.f2) OR 64 wherein R 64 represents H or (C 1 -C 3 )alkyl, or
1.2.f3) NR 65 R 66 wherein R 65 and R 66 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 65 and R 66 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 67 wherein R 67 represents H or (C 1 -C 3 )alkyl;
1.2.g) —SO 2 NR 68 R 69 wherein
R 68 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 69 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.g1) halogen;
1.2.g3) phenyl;
1.2.g4) —SO 2 CH 3 ;
1.2.g5) —OR 70 wherein R 70 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.2.g6 —NR 71 R 72 in which R 71 and R 72 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 71 and R 72 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 73 wherein R 73 represents H or (C 1 -C 3 )alkyl;
1.2.h) —N(R 74 )—SO 2 —R 75 wherein
R 74 represents H or (C 1 -C 3 )alkyl, and
R 75 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.2.h1) halogen;
1.2.h2) optionally substituted phenyl,
1.2.h3) OR 76 wherein R 76 represents H or (C 1 -C 3 )alkyl, or
1.2.h4) NR 77 R 78 wherein R 77 and R 78 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 77 and R 78 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 79 wherein R 79 represents H or (C 1 -C 3 )alkyl;
1.2.i) —NR 80 R 81 in which R 80 and R 81 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 81a wherein R 81a represents H or (C 1 -C 3 )alkyl, or R 80 and R 81 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 82 wherein R 82 represents H or (C 1 -C 3 )alkyl;
1.2.j) halogen;
1.2.k) optionally substituted phenyl;
1.2.l) NO 2 ;
1.2.m) CN; and
1.2.n) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
R 2 represents hydrogen; halogen; —(C 1 -C 5 )alkyl which may optionally bear halogen; or —(C 1 -C 3 )alkyl which may optionally bear halogen;
R 3 represents
3.1) —(C 1 -C 5 )alkyl which is substituted with
3.1.a) -halogen;
3.1.b) phenyl optionally substituted with halogen, —(C 1 -C 3 )alkyl, or —(C 1 -C 3 )alkoxy,
3.1.c) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N, optionally substituted with halogen or —(C 1 -C 3 )alkyl,
3.1.d) —CN,
3.1.e) —OR 83 wherein R 83 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
3.1.e1) halogen;
3.1.e2) optionally substituted phenyl;
3.1.e3) —S(O) 2 CH 3 ;
3.1.e4) OR 84 wherein R 84 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino; and
3.1.e5) —NR 85 R 86 in which R 85 and R 86 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 85 and R 86 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 87 wherein R 87 represents H or (C 1 -C 3 )alkyl;
3.1.f) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.1.g) —NR 89 R 90 wherein
R 89 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 90 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
3.1.g1) halogen;
3.1.g2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.1.g3) phenyl;
3.1.g4) —SO 2 CH 3 ;
3.1.g5) —OR 91 wherein R 91 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
3.1.g6) —NR 92 R 93 in which R 92 and R 93 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 92 and R 93 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 94 wherein R 94 represents H or (C 1 -C 3 )alkyl; or
3.1.g7) R 89 and R 90 may be joined and taken together with the N to which they are attached form an aromatic or nonaromatic 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 95 wherein R 95 represents H or (C 1 -C 3 )alkyl;
3.2)
wherein
R 96 represents
3.2.a) H,
3.2.b) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.2.c) —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.2.c1) halogen;
3.2.c2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.2.c3) phenyl;
3.2.c5) —OR 97 wherein R 97 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino; and
3.2.c6) —NR 98 R 99 in which R 98 and R 99 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 99a wherein R 99a represents H or (C 1 -C 3 )alkyl, or R 98 and R 99 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 100 wherein R 100 represents H or (C 1 -C 3 )alkyl;
3.3)
wherein R 101 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.3.a) halogen; and
3.3.b) phenyl;
3.4)
wherein
R 102 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 103 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.4.a) halogen;
3.4.b) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.4.c) phenyl;
3.4.d) —S(O) 2 CH 3 ;
3.4.e) OR 104 wherein R 104 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
3.4.f) —NR 105 R 106 in which R 105 and R 106 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 105 and R 106 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 107 wherein R 107 represents H or (C 1 -C 3 )alkyl;
3.6) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.7) halogen; or
3.8) —CN;
R 4 represents
4.1) —(C 1 -C 5 )alkyl which is substituted with
4.1.a) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen or OR 109 wherein R 109 represents H or (C 1 -C 3 )alkyl;
4.1.b) -halogen;
4.1.c) —OR 110 wherein R 110 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.c1) halogen;
4.1.c2) phenyl;
4.1.c4) OR 111 wherein R 111 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.c5) —NR 112 R 113 in which R 112 and R 113 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 112 and R 113 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 114 wherein R 114 represents H or (C 1 -C 3 )alkyl;
4.1.d) —NR 115 R 116 wherein
R 115 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen and
R 116 represents H, optionally substituted phenyl, or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.d1) halogen;
4.1.d2) —S(O) 2 CH 3 ;
4.1.d3) OR 117 wherein R 117 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.d4) —NR 118 R 119 in which R 118 and R 119 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 118 and R 119 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 120 wherein R 120 represents H or (C 1 -C 3 )alkyl; or
4.1.f) a 5-6 membered aromatic heterocycle containing up to two heteroatoms selected from O, S, and N;
4.2)
wherein R 121 represents —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 122 in which R 122 represents H or —(C 1 -C 3 )alkyl;
d represents 1, 2, or 3;
e represents 0 or 1;
f represents 0, 1, or 2;
4.3)
wherein R 123 represents —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 124 in which R 124 represents H or —(C 1 -C 3 )alkyl;
g represents 1, 2, or 3;
h represents 0, 1, or 2;
4.4)
wherein
R 125 represents
4.4.a) H;
4.4.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 126 in which R 126 represents H or —(C 1 -C 3 )alkyl which in turn is optionally substituted with halogen;
4.4.c) —SO 2 R 127 wherein R 127 represents optionally substituted phenyl, or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 128 wherein R 128 represents H or (C 1 -C 3 )alkyl;
4.4.d) —C(O)R 129 wherein
R 129 represents
4.4.d1) optionally substituted phenyl,
4.4.d2) —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.4.d2.1) halogen;
4.4.d2.4) —OR 130 wherein R 130 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.4.d2.5) —NR 131 R 132 in which R 131 and R 132 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 131 and R 132 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 133 wherein R 133 represents H or (C 1 -C 3 )alkyl;
4.4.d3) —OR 134 wherein R 134 represents (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.4.d4) NR 135 R 136 wherein R 135 and R 136 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 135 and R 136 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 137 wherein R 137 represents H or (C 1 -C 3 )alkyl; and
j represents 1, 2, or 3;
4.5)
wherein
X represents C or N;
R 138 represents
4.5.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
4.5.a1) halogen;
4.5.a2) OR 139 wherein R 139 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino;
4.5.a3) —NR 140 R 141 in which R 140 and R 141 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 141a wherein R 141a represents H or (C 1 -C 3 )alkyl, or R 140 and R 141 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 142 wherein R 142 represents H or (C 1 -C 3 )alkyl; and
4.5.a4) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
4.5.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
4.5.b1) halogen;
4.5.c) OR 144 wherein
R 144 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
4.5.c1) halogen;
4.5.c2) OR 145 wherein R 145 represents H or (C 1 -C 3 )alkyl which may optionally bear (C 1 -C 3 )mono- or di-alkylamino; and
4.5.c3) NR 146 R 147 in which R 146 and R 1473 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 146 and R 147 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 148 wherein R 148 represents H or (C 1 -C 3 )alkyl;
4.5.e) —C(O)—NR 150 R 151 wherein
R 150 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 151 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.e1) halogen;
4.5.e3) phenyl;
4.5.e4) —SO 2 CH 3 ;
4.5.e5) —OR 152 wherein R 152 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.5.e6) —NR 153 R 154 in which R 153 and R 154 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 153 and R 154 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 155 wherein R 155 represents H or (C 1 -C 3 )alkyl;
4.5.f) —N(R 156 )—C(O)—R 157 wherein
R 156 represents H or (C 1 -C 3 )alkyl; and
R 157 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
4.5.f1) optionally substituted phenyl,
4.5.f2) OR 158 wherein R 158 represents H or (C 1 -C 3 )alkyl, or
4.5.f3) NR 159 R 160 wherein R 159 and R 160 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 159 and R 160 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 161 wherein R 161 represents H or (C 1 -C 3 )alkyl;
4.5.g) —SO 2 NR 162 R 163 wherein
R 162 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 163 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.g1) halogen;
4.5.g3) phenyl;
4.5.g4) —SO 2 CH 3 ;
4.5.g5) —OR 164 wherein R 164 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.5.g6) —NR 165 R 166 in which R 165 and R 166 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 165 and R 166 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 167 wherein R 167 represents H or (C 1 -C 3 )alkyl;
4.5.h) —N(R 168 )—SO 2 —R 169 wherein
R 168 represents H or (C 1 -C 3 )alkyl, and
R 169 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
4.5.h1) halogen,
4.5.h2) optionally substituted phenyl,
4.5.h3) OR 170 wherein R 170 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen, or
4.5.h4) NR 171 R 172 wherein R 171 and R 172 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 171 and R 172 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 173 wherein R 173 represents H or (C 1 -C 3 )alkyl;
4.5.i) —NR 174 R 175 in which R 174 and R 175 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 175a wherein R 175a represents H or (C 1 -C 3 )alkyl, or R 174 and R 175 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 176 wherein R 176 represents H or (C 1 -C 3 )alkyl;
4.5.j) halogen;
4.5.l) NO 2 ;
4.5.m) CN; or
4.5.n) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N; and
k represents 0, 1, or 2;
4.6)
wherein R 177 represents H or —(C 1 -C 3 )alkyl; and
m represents 1, 2, or 3;
4.7)
wherein
n represents 1, 2, or 3; and
p represents 0, 1, or 2;
4.8)
wherein
q represents 1, 2, or 3;
4.9)
wherein
R 178 represents
4.9.a) H;
4.9.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 179 in which R 179 represents H or (C 1 -C 3 )alkyl optionally substituted with halogen;
4.9.c) —SO 2 R 180 wherein R 180 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl, which may be substituted with halogen or —OR 181 wherein R 181 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.9.d) —C(O)R 182 wherein R 182 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.9.d1) halogen;
4.9.d2) optionally substituted phenyl;
4.9.d4) OR 183 wherein R 183 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.9.d5) —NR 184 R 185 in which R 184 and R 185 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 185a wherein R 185a represents H or (C 1 -C 3 )alkyl, or R 184 and R 185 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 186 wherein R 186 represents H or (C 1 -C 3 )alkyl;
4.9e) —C(O)OR 187 wherein R 187 represents (C 1 -C 3 )alkyl; or
4.9.f) —C(O)—NR 188 R 189 wherein R 188 and R 189 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 188 and R 189 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 190 wherein R 190 represents H or (C 1 -C 3 )alkyl;
r represents 0, 1, or 2; and
s represents 0 or 1;
4.10)
wherein
R 191 represents
4.10.a) H;
4.10.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 192 in which R 192 represents H or (C 1 -C 3 )alkyl;
4.10c) —SO 2 R 193 wherein R 193 represents phenyl or —(C 1 -C 3 )alkyl, both of which may be substituted with halogen or —(C 1 -C 3 )alkyl;
4.10.d) —C(O)R 194 wherein R 194 represents (C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.10.d1) halogen;
4.10.d2) phenyl;
4.10.d4) OR 195 wherein R 195 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.10.d5) —NR 196 R 197 in which R 196 and R 197 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 197a wherein R 197a represents H or (C 1 -C 3 )alkyl, or R 196 and R 197 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 198 wherein R 198 represents H or (C 1 -C 3 )alkyl;
4.10.e) —C(O)OR 199 wherein R 199 represents (C 1 -C 3 )alkyl; or
4.10.f) —C(O)—NR 200 R 201 wherein R 200 and R 201 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 200 and R 201 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 202 wherein R 202 represents H or (C 1 -C 3 )alkyl; and
X represents O, S, S(O) 2 , or NR 203 wherein
R 203 represents H or —(C 1 -C 3 )alkyl; and
t represents 0, 1, or 2;
4.11) halogen; or
4.12) —CN;
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 wherein in formula (I)
R 1 represents
1.1) phenyl which may optionally bear up to 4 substituents independently selected from the group consisting of
1.1.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.1.a1) halogen;
1.1.a2) OR 5 wherein R 5 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.1.a3) —NR 6 R 7 in which R 6 and R 7 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or R 6 and R 7 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 8 wherein R 8 represents H or (C 1 -C 3 )alkyl; and
1.1.a4) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
1.1.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.1.b1) halogen;
1.1.c) OR 10 wherein
R 10 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.1.c1) halogen;
1.1.c2) OR 11 wherein R 11 represents H or (C 1 -C 3 )alkyl; and
1.1.c3) NR 12 R 13 in which R 12 and R 13 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 12 and R 13 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 14 wherein R 14 represents H or (C 1 -C 3 )alkyl;
1.1.e) —C(O)—NR 16 R 17 wherein
R 16 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 17 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.1.e1) halogen;
1.1.e5) —OR 18 wherein R 18 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.e6) —NR 19 R 20 in which R 19 and R 20 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 19 and R 20 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 21 wherein R 21 represents H or (C 1 -C 3 )alkyl;
1.1.f) —N(R 22 )—C(O)—R 23 wherein
R 22 represents H or (C 1 -C 3 )alkyl; and
R 23 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl;
1.1.g) —SO 2 NR 28 R 29 wherein
R 28 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 29 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with:
1.1.g1) halogen;
1.1.g4) —SO 2 CH 3 ;
1.1.g5) —OR 30 wherein R 30 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.g6) —NR 31 R 32 in which R 31 and R 32 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 31 and R 32 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 33 wherein R 33 represents H or (C 1 -C 3 )alkyl;
1.1.h) —N(R 34 )—SO 2 —R 35 wherein
R 34 represents H or (C 1 -C 3 )alkyl, and
R 35 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.1.h1) halogen;
1.1.i) —NR 40 R 41 in which R 40 and R 41 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 42 in which R 42 represents H or (C 1 -C 3 )alkyl, or R 40 and R 41 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 43 wherein R 43 represents H or (C 1 -C 3 )alkyl;
1.1.j) halogen;
1.1.l) NO 2 ;
1.1.m) CN; and
1.1.n) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
or
R 1 represents
1.2) a 5-6 membered aromatic heterocycle selected from imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, and furan; said R 1 heterocycle optionally bearing up to 4 substituents independently selected from the group consisting of
1.2.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.2.a1) halogen;
1.2.a2) OR 45 wherein R 45 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.a3) —NR 46 R 47 in which R 46 and R 47 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 46 and R 47 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 48 wherein R 48 represents H or (C 1 -C 3 )alkyl; and
1.2.a4) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
1.2.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.2.b1) halogen;
1.2.c) OR 50 wherein
R 50 represents H; phenyl; benzyl; —(C 3 -C 6 )cycloalkyl; or —(C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.2.c1) halogen;
1.2.e) —C(O)—NR 56 R 57 wherein
R 56 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 57 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.e1) halogen; or
1.2.e5) —OR 58 wherein R 58 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.f) —N(R 62 )—C(O)—R 63 wherein
R 62 represents H or (C 1 -C 3 )alkyl; and
R 63 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl;
1.2.g) —SO 2 NR 68 R 69 wherein
R 68 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 69 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.g1) halogen; or
1.2.g5) —OR 70 wherein R 70 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.h) —N(R 74 )—SO 2 —R 75 wherein
R 74 represents H or (C 1 -C 3 )alkyl, and
R 75 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.2.h1) halogen;
1.2.i) —NR 80 R 81 in which R 80 and R 81 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 81a wherein R 81a represents H or (C 1 -C 3 )alkyl, or R 80 and R 81 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 82 wherein R 82 represents H or (C 1 -C 3 )alkyl;
1.2.j) halogen;
1.2.k) optionally substituted phenyl;
1.2.l) NO 2 ;
1.2.m) CN; and
1.2.n) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
R 2 represents hydrogen; halogen; —(C 1 -C 5 )alkyl which may optionally bear halogen; or —O(C 1 -C 3 )alkyl which may optionally bear halogen;
R 3 represents
3.1) —(C 1 -C 5 )alkyl which is substituted with
3.1.a) -halogen;
3.1.b) phenyl optionally substituted with halogen, —(C 1 -C 3 )alkyl, or —(C 1 -C 3 )alkoxy,
3.1.c) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N, optionally substituted with halogen or —(C 1 -C 3 )alkyl,
3.1.d) —CN,
3.1.e) —OR 83 wherein R 83 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
3.1.e1) halogen;
3.1.e2) optionally substituted phenyl;
3.1.e3) —S(O) 2 CH 3 ;
3.1.e4) OR 84 wherein R 84 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino; and
3.1.e5) —NR 85 R 86 in which R 85 and R 86 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 85 and R 86 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 87 wherein R 87 represents H or (C 1 -C 3 )alkyl;
3.1.f) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.1.g) —NR 89 R 90 wherein
R 89 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 90 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
3.1.g1) halogen;
3.1.g2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.1.g3) phenyl;
3.1.g4) —SO 2 CH 3 ;
3.1.g5) —OR 91 wherein R 91 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
3.1.g6) —NR 92 R 93 in which R 92 and R 93 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 92 and R 93 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 94 wherein R 94 represents H or (C 1 -C 3 )alkyl; or
3.1.g7) R 89 and R 90 may be joined and taken together with the N to which they are attached form an aromatic or nonaromatic 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 95 wherein R 95 represents H or (C 1 -C 3 )alkyl;
3.2)
wherein
R 96 represents
3.2.a) H,
3.2.b) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.2.c) —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.2.c1) halogen;
3.2.c2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.2.c3) phenyl;
3.2.c5) —OR 97 wherein R 97 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino; and
3.2.c6) —NR 98 R 99 in which R 98 and R 99 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 99a wherein R 99a represents H or (C 1 -C 3 )alkyl, or R 98 and R 99 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 100 wherein R 100 represents H or (C 1 -C 3 )alkyl;
3.3)
wherein R 101 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.3.a) halogen; and
3.3.b) phenyl;
3.4)
wherein
R 102 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 103 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.4.a) halogen;
3.4.b) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.4.c) phenyl;
3.4.d) —S(O) 2 CH 3 ;
3.4.e) OR 104 wherein R 104 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
3.4.f) —NR 105 R 106 in which R 105 and R 106 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 105 and R 106 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 107 wherein R 107 represents H or (C 1 -C 3 )alkyl;
3.6) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.7) halogen; or
3.8) —CN;
R 4 represents
4.1) —(C 1 -C 5 )alkyl which is substituted with
4.1.a) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen or OR 109 wherein R 109 represents H or (C 1 -C 3 )alkyl;
4.1.b) -halogen;
4.1.c) —OR 110 wherein R 110 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.c1) halogen;
4.1.c2) phenyl;
4.1.c4) OR 111 wherein R 111 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.c5) —NR 112 R 113 in which R 112 and R 113 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 112 and R 113 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 114 wherein R 114 represents H or (C 1 -C 3 )alkyl;
4.1.d) —NR 115 R 116 wherein
R 115 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen and
R 116 represents H, optionally substituted phenyl, or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.d1) halogen;
4.1.d2) —S(O) 2 CH 3 ;
4.1.d3) OR 117 wherein R 117 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.d4) —NR 118 R 119 in which R 118 and R 119 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 118 and R 119 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 120 wherein R 120 represents H or (C 1 -C 3 )alkyl; or
4.1.f) a 5-6 membered aromatic heterocycle containing up to two heteroatoms selected from O, S, and N;
4.2)
wherein R 121 represents —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 122 in which R 122 represents H or —(C 1 -C 3 )alkyl;
d represents 1, 2, or 3;
e represents 0 or 1;
f represents 0, 1, or 2;
4.3)
wherein R 123 represents —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 124 in which R 124 represents H or —(C 1 -C 3 )alkyl;
g represents 1, 2, or 3;
h represents 0, 1, or 2;
4.4)
wherein
R 125 represents
4.4.a) H;
4.4.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 126 in which R 126 represents H or —(C 1 -C 3 )alkyl which in turn is optionally substituted with halogen;
4.4.c) —SO 2 R 127 wherein R 127 represents optionally substituted phenyl, or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 128 wherein R 128 represents H or (C 1 -C 3 )alkyl;
4.4.d) —C(O)R 129 wherein
R 129 represents
4.4.d1) optionally substituted phenyl,
4.4.d2) —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.4.d2.1) halogen;
4.4.d2.4) —OR 130 wherein R 130 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.4.d2.5) —NR 131 R 132 in which R 131 and R 132 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 131 and R 132 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 133 wherein R 133 represents H or (C 1 -C 3 )alkyl;
4.4.d3) —OR 134 wherein R 134 represents (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.4.d4) NR 135 R 136 wherein R 135 and R 136 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 135 and R 136 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 137 wherein R 137 represents H or (C 1 -C 3 )alkyl; and
j represents 1, 2, or 3;
4.5)
wherein
X represents C or N;
R 138 represents
4.5.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
4.5.a1) halogen;
4.5.a2) OR 139 wherein R 139 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino;
4.5.a3) —NR 140 R 141 in which R 140 and R 141 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 141a wherein R 141a represents H or (C 1 -C 3 )alkyl, or R 140 and R 141 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 142 wherein R 142 represents H or (C 1 -C 3 )alkyl; and
4.5.a4) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
4.5.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
4.5.b1) halogen;
4.5.c) OR 144 wherein
R 144 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
4.5.c1) halogen;
4.5.c2) OR 145 wherein R 145 represents H or (C 1 -C 3 )alkyl which may optionally bear (C 1 -C 3 )mono- or di-alkylamino; and
4.5.c3) NR 146 R 147 in which R 146 and R 1473 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 146 and R 147 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 148 wherein R 148 represents H or (C 1 -C 3 )alkyl;
4.5.e) —C(O)—NR 150 R 151 wherein
R 150 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 151 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.e1) halogen;
4.5.e3) phenyl;
4.5.e4) —SO 2 CH 3 ;
4.5.e5) —OR 152 wherein R 152 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.5.e6) —NR 153 R 154 in which R 153 and R 154 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 153 and R 154 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 155 wherein R 155 represents H or (C 1 -C 3 )alkyl;
4.5.f) —N(R 156 )—C(O)—R 157 wherein
R 156 represents H or (C 1 -C 3 )alkyl; and
R 157 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
4.5.f1) optionally substituted phenyl,
4.5.f2) OR 158 wherein R 158 represents H or (C 1 -C 3 )alkyl, or
4.5.f3) NR 159 R 160 wherein R 159 and R 160 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 159 and R 160 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 161 wherein R 161 represents H or (C 1 C 3 )alkyl;
4.5.g) —SO 2 NR 162 R 163 wherein
R 162 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 163 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.g1) halogen;
4.5.g3) phenyl;
4.5.g4) —SO 2 CH 3 ;
4.5.g5) —OR 164 wherein R 164 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.5.g6) —NR 165 R 166 in which R 165 and R 166 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 165 and R 166 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 167 wherein R 167 represents H or (C 1 -C 3 )alkyl;
4.5.h) —N(R 168 )—SO 2 —R 169 wherein
R 168 represents H or (C 1 -C 3 )alkyl, and
R 169 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
4.5.h1) halogen,
4.5.h2) optionally substituted phenyl,
4.5.h3) OR 170 wherein R 170 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen, or
4.5.h4) NR 171 R 172 wherein R 171 and R 172 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 171 and R 172 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 173 wherein R 173 represents H or (C 1 C 3 )alkyl;
4.5.i) —NR 174 R 175 in which R 174 and R 175 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 175a wherein R 175a represents H or (C 1 -C 3 )alkyl, or R 174 and R 175 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 176 wherein R 176 represents H or (C 1 -C 3 )alkyl;
4.5.j) halogen;
4.5.l) NO 2 ;
4.5.m) CN; or
4.5.n) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N; and
k represents 0, 1, or 2;
4.6)
wherein R 177 represents H or —(C 1 -C 3 )alkyl; and
m represents 1, 2, or 3;
4.7)
wherein
n represents 1, 2, or 3; and
p represents 0, 1, or 2;
4.8)
wherein
q represents 1, 2, or 3;
4.9)
wherein
R 178 represents
4.9.a) H;
4.9.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 179 in which R 179 represents H or (C 1 -C 3 )alkyl optionally substituted with halogen;
4.9.c) —SO 2 R 180 wherein R 180 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl, which may be substituted with halogen or —OR 181 wherein R 181 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.9.d) —C(O)R 182 wherein R 182 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.9.d1) halogen;
4.9.d2) optionally substituted phenyl;
4.9.d4) OR 183 wherein R 183 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.9.d5) —NR 184 R 185 in which R 184 and R 185 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 185a wherein R 185a represents H or (C 1 -C 3 )alkyl, or R 184 and R 185 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 186 wherein R 186 represents H or (C 1 -C 3 )alkyl;
4.9e) —C(O)OR 187 wherein R 187 represents (C 1 -C 3 )alkyl; or
4.9.f) —C(O)—NR 188 R 189 wherein R 188 and R 189 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 188 and R 189 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 190 wherein R 190 represents H or (C 1 -C 3 )alkyl;
r represents 0, 1, or 2; and
s represents 0 or 1;
4.10)
wherein
R 191 represents
4.10.a) H;
4.10.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 192 in which R 192 represents H or (C 1 -C 3 )alkyl;
4.10c) —SO 2 R 193 wherein R 193 represents phenyl or —(C 1 -C 3 )alkyl, both of which may be substituted with halogen or —(C 1 -C 3 )alkyl;
4.10.d) —C(O)R 194 wherein R 194 represents (C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.10.d1) halogen;
4.10.d2) phenyl;
4.10.d4) OR 195 wherein R 195 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.10.d5) —NR 196 R 197 in which R 196 and R 197 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 197a wherein R 197a represents H or (C 1 -C 3 )alkyl, or R 196 and R 197 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 198 wherein R 198 represents H or (C 1 -C 3 )alkyl;
4.10.e) —C(O)OR 199 wherein R 199 represents (C 1 -C 3 )alkyl; or
4.10.f) —C(O)—NR 200 R 201 wherein R 200 and R 201 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 200 and R 201 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 202 wherein R 202 represents H or (C 1 -C 3 )alkyl; and
X represents O, S, S(O) 2 , or NR 203 wherein
R 203 represents H or —(C 1 -C 3 )alkyl; and
t represents 0, 1, or 2;
4.11) halogen; or
4.12) —CN;
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 wherein in formula (I)
R 1 represents
1.1) phenyl which may optionally bear up to 4 substituents independently selected from the group consisting of
1.1.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.1.a1) halogen;
1.1.a2) OR 5 wherein R 5 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.1.a3) —NR 6 R 7 in which R 6 and R 7 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or R 6 and R 7 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 8 wherein R 8 represents H or (C 1 -C 3 )alkyl; and
1.1.a4) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
1.1.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.1.b1) halogen;
1.1.c) OR 10 wherein
R 10 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.1.c1) halogen;
1.1.c2) OR 11 wherein R 11 represents H or (C 1 -C 3 )alkyl; and
1.1.c3) NR 12 R 13 in which R 12 and R 13 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 12 and R 13 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 14 wherein R 14 represents H or (C 1 -C 3 )alkyl;
1.1.e) —O(O)—NR 16 R 17 wherein
R 16 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 17 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.1.e1) halogen;
1.1.e5) —OR 18 wherein R 18 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.e6) —NR 19 R 20 in which R 19 and R 20 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 19 and R 20 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 21 wherein R 21 represents H or (C 1 -C 3 )alkyl;
1.1.f) —N(R 22 ) —C(O)—R 23 wherein
R 22 represents H or (C 1 -C 3 )alkyl; and
R 23 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl;
1.1.g) —SO 2 NR 28 R 29 wherein
R 28 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 29 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with:
1.1.g1) halogen;
1.1.g4) —SO 2 CH 3 ;
1.1.g5) —OR 30 wherein R 30 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.g6) —NR 31 R 32 in which R 31 and R 32 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 31 and R 32 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 33 wherein R 33 represents H or (C 1 -C 3 )alkyl;
1.1.h) —N(R 34 )—SO 2 —R 35 wherein
R 34 represents H or (C 1 -C 3 )alkyl, and
R 35 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.1.h1) halogen;
1.1.i) —NR 40 R 41 in which R 40 and R 41 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 42 in which R 42 represents H or (C 1 -C 3 )alkyl, or R 40 and R 41 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 43 wherein R 43 represents H or (C 1 -C 3 )alkyl;
1.1.j) halogen;
1.1.l) NO 2 ;
1.1.m) CN; and
1.1.n) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
or
R 1 represents
1.2) a 5-6 membered aromatic heterocycle selected from imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, and furan; said R 1 heterocycle optionally bearing up to 4 substituents independently selected from the group consisting of
1.2.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.2.a1) halogen;
1.2.a2) OR 45 wherein R 45 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.a3) —NR 46 R 47 in which R 46 and R 47 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 46 and R 47 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 48 wherein R 48 represents H or (C 1 -C 3 )alkyl; and
1.2.a4) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
1.2.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.2.b1) halogen;
1.2.c) OR 50 wherein
R 50 represents H; phenyl; benzyl; —(C 3 -C 6 )cycloalkyl; or —(C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.2.c1) halogen;
1.2.e) —C(O)—NR 56 R 57 wherein
R 56 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 57 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.e1) halogen; or
1.2.e5) —OR 58 wherein R 58 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.f) —N(R 62 )—C(O)—R 63 wherein
R 62 represents H or (C 1 -C 3 )alkyl; and
R 63 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl;
1.2.g) —SO 2 NR 68 R 69 wherein
R 68 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 69 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.g1) halogen; or
1.2.g5) —OR 70 wherein R 70 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.h) —N(R 74 )—SO 2 —R 75 wherein
R 74 represents H or (C 1 -C 3 )alkyl, and
R 75 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.2.h1) halogen;
1.2.i) —NR 80 R 81 in which R 80 and R 81 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 81a wherein R 81a represents H or (C 1 -C 3 )alkyl, or R 80 and R 81 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 82 wherein R 82 represents H or (C 1 -C 3 )alkyl;
1.2.j) halogen;
1.2.k) optionally substituted phenyl;
1.2.l) NO 2 ;
1.2.m) CN; and
1.2.n) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
R 2 represents hydrogen; halogen; —(C 1 -C 5 )alkyl which may optionally bear halogen; or —O(C 1 -C 3 )alkyl which may optionally bear halogen;
R 3 represents
3.1) —(C 1 -C 5 )alkyl which is optionally substituted with
3.1.a) -halogen;
3.1.c) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N, optionally substituted with halogen or —(C 1 -C 3 )alkyl;
3.1.d) —CN;
3.1.e) —OR 83 wherein R 83 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
3.1.e1) halogen; or
3.1.e4) OR 84 wherein R 84 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
3.1.f) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.1.g) —NR 89 R 90 wherein
R 89 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 90 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
3.1.g1) halogen;
3.1.g4) —SO 2 CH 3 ;
3.1.g5) —OR 91 wherein R 91 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
3.1.g7) R 89 and R 90 may be joined and taken together with the N to which they are attached form an aromatic or nonaromatic 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 95 wherein R 95 represents H or (C 1 -C 3 )alkyl;
3.2)
wherein
R 96 represents
3.2.b) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.2.c) —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.2.c1) halogen; and
3.2.c5) —OR 97 wherein R 97 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
3.3)
wherein R 101 represents H or —(C 1 -C 5 )alkyl;
3.4)
wherein
R 102 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 103 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.4.a) halogen;
3.4.d) —S(O) 2 CH 3 ; and
3.4.e) OR 104 wherein R 104 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
3.7) halogen; or
3.8) —CN;
R 4 represents
4.1) —(C 1 -C 5 )alkyl which is optionally substituted with
4.1.a) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen or OR 109 wherein R 109 represents H or (C 1 -C 3 )alkyl;
4.1.b) -halogen;
4.1.c) —OR 110 wherein R 110 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.c1) halogen;
4.1.c2) phenyl;
4.1.c4) OR 111 wherein R 111 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.c5) —NR 112 R 113 in which R 112 and R 113 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 112 and R 113 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 114 wherein R 114 represents H or (C 1 -C 3 )alkyl;
4.1.d) —NR 115 R 116 wherein
R 115 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen and
R 116 represents H, optionally substituted phenyl, or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.d1) halogen;
4.1.d2) —S(O) 2 CH 3 ;
4.1.d3) OR 117 wherein R 117 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.d4) —NR 118 R 119 in which R 118 and R 119 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 118 and R 119 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 120 wherein R 120 represents H or (C 1 -C 3 )alkyl; or
4.1.f) a 5-6 membered aromatic heterocycle containing up to two heteroatoms selected from O, S, and N;
4.2)
wherein R 121 represents —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 122 in which R 122 represents H or —(C 1 -C 3 )alkyl;
d represents 1, 2, or 3;
e represents 0 or 1;
f represents 0, 1, or 2;
4.3)
wherein R 123 represents —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 124 in which R 124 represents H or —(C 1 -C 3 )alkyl;
g represents 1, 2, or 3;
h represents 0, 1, or 2;
4.4)
wherein
R 125 represents
4.4.a) H;
4.4.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 126 in which R 126 represents H or —(C 1 -C 3 )alkyl which in turn is optionally substituted with halogen;
4.4.c) —SO 2 R 127 wherein R 127 represents optionally substituted phenyl, or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 128 wherein R 128 represents H or (C 1 -C 3 )alkyl;
4.4.d) —C(O)R 129 wherein
R 129 represents
4.4.d1) optionally substituted phenyl,
4.4.d2) —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.4.d2.1) halogen;
4.4.d2.4) —OR 130 wherein R 130 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.4.d2.5) —NR 131 R 132 in which R 131 and R 132 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 131 and R 132 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 133 wherein R 133 represents H or (C 1 -C 3 )alkyl;
4.4.d3) —OR 134 wherein R 134 represents (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.4.d4) NR 135 R 136 wherein R 135 and R 136 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 135 and R 136 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 137 wherein R 137 represents H or (C 1 -C 3 )alkyl; and
j represents 1, 2, or 3;
4.5)
wherein
X represents C or N;
R 138 represents
4.5.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
4.5.a1) halogen;
4.5.a2) OR 139 wherein R 139 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino;
4.5.a3) —NR 140 R 141 in which R 140 and R 141 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 141a wherein R 141a represents H or (C 1 -C 3 )alkyl, or R 140 and R 141 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 142 wherein R 142 represents H or (C 1 -C 3 )alkyl; and
4.5.a4) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
4.5.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
4.5.b1) halogen;
4.5.c) OR 144 wherein
R 144 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
4.5.c1) halogen;
4.5.c2) OR 145 wherein R 145 represents H or (C 1 -C 3 )alkyl which may optionally bear (C 1 -C 3 )mono- or di-alkylamino; and
4.5.c3) NR 146 R 147 in which R 146 and R 1473 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 146 and R 147 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 148 wherein R 148 represents H or (C 1 -C 3 )alkyl;
4.5.e) —C(O)—NR 150 R 151 wherein
R 150 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 151 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.e1) halogen;
4.5.e3) phenyl;
4.5.e4) —SO 2 CH 3 ;
4.5.e5) —OR 152 wherein R 152 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.5.e6) —NR 153 R 154 in which R 153 and R 154 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 153 and R 154 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 155 wherein R 155 represents H or (C 1 C 3 )alkyl;
4.5.f) —N(R 156 )—C(O)—R 157 wherein
R 156 represents H or (C 1 -C 3 )alkyl; and
R 157 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
4.5.f1) optionally substituted phenyl,
4.5.f2) OR 158 wherein R 158 represents H or (C 1 -C 3 )alkyl, or
4.5.f3) NR 159 R 160 wherein R 159 and R 160 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 159 and R 160 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 161 wherein R 161 represents H or (C 1 -C 3 )alkyl;
4.5.g) —SO 2 NR 162 R 163 wherein
R 162 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 163 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.g1) halogen;
4.5.g3) phenyl;
4.5.g4) —SO 2 CH 3 ;
4.5.g5) —OR 164 wherein R 164 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
4.5.g6) —NR 165 R 166 in which R 165 and R 166 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 165 and R 166 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 167 wherein R 167 represents H or (C 1 -C 3 )alkyl;
4.5.h) —N(R 168 )—SO 2 —R 169 wherein
R 168 represents H or (C 1 -C 3 )alkyl, and
R 169 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
4.5.h1) halogen,
4.5.h2) optionally substituted phenyl,
4.5.h3) OR 170 wherein R 170 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen, or
4.5.h4) —NR 171 R 172 wherein R 171 and R 172 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 171 and R 172 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 13 wherein R 173 represents H or (C 1 -C 3 )alkyl;
4.5.i) —NR 174 R 175 in which R 174 and R 175 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 175a wherein R 175a represents H or (C 1 -C 3 )alkyl, or R 174 and R 175 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 176 wherein R 176 represents H or (C 1 -C 3 )alkyl;
4.5.j) halogen;
4.5.l) NO 2 ;
4.5.m) CN; or
4.5.n) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N; and
k represents 0, 1, or 2;
4.6)
wherein R 177 represents H or —(C 1 -C 3 )alkyl; and
m represents 1, 2, or 3;
4.7)
wherein
n represents 1, 2, or 3; and
p represents 0, 1, or 2;
4.8)
wherein
q represents 1, 2, or 3;
4.9)
wherein
R 178 represents
4.9.a) H;
4.9.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 179 in which R 179 represents H or (C 1 -C 3 )alkyl optionally substituted with halogen;
4.9.c) —SO 2 R 180 wherein R 180 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl, which may be substituted with halogen or —OR 181 wherein R 181 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.9.d) —C(O)R 182 wherein R 182 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.9.d1) halogen;
4.9.d2) optionally substituted phenyl;
4.9.d4) OR 183 wherein R 183 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.9.d5) —NR 184 R 185 in which R 184 and R 185 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 185a wherein R 185a represents H or (C 1 -C 3 )alkyl, or R 184 and R 185 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 186 wherein R 186 represents H or (C 1 -C 3 )alkyl;
4.9e) —C(O)OR 187 wherein R 187 represents (C 1 -C 3 )alkyl; or
4.9.f) —C(O)—NR 188 R 189 wherein R 188 and R 189 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 188 and R 189 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 190 wherein R 190 represents H or (C 1 -C 3 )alkyl;
r represents 0, 1, or 2; and
s represents 0 or 1;
4.10)
wherein
R 191 represents
4.10.a) H;
4.10.b) —(C 1 -C 3 )alkyl which may optionally bear halogen or —OR 192 in which R 192 represents H or (C 1 -C 3 )alkyl;
4.10c) —SO 2 R 193 wherein R 193 represents phenyl or —(C 1 -C 3 )alkyl, both of which may be substituted with halogen or —(C 1 -C 3 )alkyl;
4.10.d) —C(O)R 194 wherein R 194 represents (C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.10.d1) halogen;
4.10.d2) phenyl;
4.10.d4) OR 195 wherein R 195 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.10.d5) —NR 196 R 197 in which R 196 and R 197 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 197a wherein R 197a represents H or (C 1 -C 3 )alkyl, or R 196 and R 197 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 198 wherein R 198 represents H or (C 1 -C 3 )alkyl;
4.10.e) —C(O)OR 199 wherein R 199 represents (C 1 -C 3 )alkyl; or
4.10.f) —C(O)—NR 200 R 201 wherein R 200 and R 201 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 200 and R 201 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 202 wherein R 202 represents H or (C 1 -C 3 )alkyl; and
X represents O, S, S(O) 2 , or NR 203 wherein
R 203 represents H or —(C 1 -C 3 )alkyl; and
t represents 0, 1, or 2;
4.11) halogen; or
4.12) —CN;
or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 wherein in formula (I)
R 1 represents
1.1) phenyl which may optionally bear up to 4 substituents independently selected from the group consisting of
1.1.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.1.a1) halogen;
1.1.a2) OR 5 wherein R 5 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.1.a3) —NR 6 R 7 in which R 6 and R 7 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or R 6 and R 7 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 8 wherein R 8 represents H or (C 1 -C 3 )alkyl; and
1.1.a4) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
1.1.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.1.b1) halogen;
1.1.c) OR 10 wherein
R 10 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.1.c1) halogen;
1.1.c2) OR 11 wherein R 11 represents H or (C 1 -C 3 )alkyl; and
1.1.c3) NR 12 R 13 in which R 12 and R 13 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 12 and R 13 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 14 wherein R 14 represents H or (C 1 -C 3 )alkyl;
1.1.e) —O(O)—NR 16 R 17 wherein
R 16 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 17 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.1.e1) halogen;
1.1.e5) —OR 18 wherein R 18 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.e6) —NR 19 R 20 in which R 19 and R 20 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 19 and R 20 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 21 wherein R 21 represents H or (C 1 -C 3 )alkyl;
1.1.f) —N(R 22 )—C(O)—R 23 wherein
R 22 represents H or (C 1 -C 3 )alkyl; and
R 23 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl;
1.1.g) —SO 2 NR 28 R 29 wherein
R 28 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 29 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with:
1.1.g1) halogen;
1.1.g4) —SO 2 CH 3 ;
1.1.g5) —OR 30 wherein R 30 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.g6) —NR 31 R 32 in which R 31 and R 32 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 31 and R 32 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 33 wherein R 33 represents H or (C 1 -C 3 )alkyl;
1.1.h) —N(R 34 )—SO 2 —R 35 wherein
R 34 represents H or (C 1 -C 3 )alkyl, and
R 35 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.1.h1) halogen;
1.1.i) —NR 40 R 41 in which R 40 and R 41 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 42 in which R 42 represents H or (C 1 -C 3 )alkyl, or R 40 and R 41 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 43 wherein R 43 represents H or (C 1 -C 3 )alkyl;
1.1.j) halogen;
1.1.l) NO 2 ;
1.1.m) CN; and
1.1.n) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
or
R 1 represents
1.2) a 5-6 membered aromatic heterocycle selected from imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, and furan; said R 1 heterocycle optionally bearing up to 4 substituents independently selected from the group consisting of
1.2.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.2.a1) halogen;
1.2.a2) OR 45 wherein R 45 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.a3) —NR 46 R 47 in which R 46 and R 47 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 46 and R 47 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 48 wherein R 48 represents H or (C 1 -C 3 )alkyl; and
1.2.a4) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
1.2.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.2.b1) halogen;
1.2.c) OR 50 wherein
R 50 represents H; phenyl; benzyl; —(C 3 -C 6 )cycloalkyl; or —(C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.2.c1) halogen;
1.2.e) —C(O)—NR 56 R 57 wherein
R 56 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 57 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.e1) halogen; or
1.2.e5) —OR 58 wherein R 58 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.f) —N(R 62 )—C(O)—R 63 wherein
R 62 represents H or (C 1 -C 3 )alkyl; and
R 63 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl;
1.2.g) —SO 2 NR 68 R 69 wherein
R 68 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 69 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.g1) halogen; or
1.2.g5) —OR 70 wherein R 70 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.2.h) —N(R 74 )—SO 2 —R 75 wherein
R 74 represents H or (C 1 -C 3 )alkyl, and
R 75 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.2.h1) halogen;
1.2.i) —NR 80 R 81 in which R 80 and R 81 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 81a wherein R 81a represents H or (C 1 -C 3 )alkyl, or R 80 and R 81 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 82 wherein R 82 represents H or (C 1 -C 3 )alkyl;
1.2.j) halogen;
1.2.k) optionally substituted phenyl;
1.2.l) NO 2 ;
1.2.m) CN; and
1.2.n) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
R 2 represents hydrogen; halogen; —(C 1 -C 5 )alkyl which may optionally bear halogen; or —O(C 1 -C 3 )alkyl which may optionally bear halogen;
R 3 represents
3.1) —(C 1 -C 5 )alkyl which is substituted with
3.1.a) -halogen;
3.1.b) phenyl optionally substituted with halogen, —(C 1 -C 3 )alkyl, or —(C 1 -C 3 )alkoxy,
3.1.c) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N, optionally substituted with halogen or —(C 1 -C 3 )alkyl,
3.1.d) —CN,
3.1.e) —OR 83 wherein R 83 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
3.1.e1) halogen;
3.1.e2) optionally substituted phenyl;
3.1.e3) —S(O) 2 CH 3 ;
3.1.e4) OR 84 wherein R 84 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino; and
3.1.e5) —NR 85 R 86 in which R 85 and R 86 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 85 and R 86 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 87 wherein R 87 represents H or (C 1 -C 3 )alkyl;
3.1.f) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.1.g) —NR 89 R 90 wherein
R 89 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 90 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
3.1.g1) halogen;
3.1.g2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.1.g3) phenyl;
3.1.g4) —SO 2 CH 3 ;
3.1.g5) —OR 91 wherein R 91 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
3.1.g6) —NR 92 R 93 in which R 92 and R 93 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 92 and R 93 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 94 wherein R 94 represents H or (C 1 -C 3 )alkyl; or
3.1.g7) R 89 and R 90 may be joined and taken together with the N to which they are attached form an aromatic or nonaromatic 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 95 wherein R 95 represents H or (C 1 -C 3 )alkyl;
3.2)
wherein
R 96 represents
3.2.a) H,
3.2.b) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.2.c) —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.2.c1) halogen;
3.2.c2) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.2.c3) phenyl;
3.2.c5) —OR 97 wherein R 97 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen or —(C 1 -C 3 )mono- or di-alkylamino; and
3.2.c6) —NR 98 R 99 in which R 98 and R 99 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 99a wherein R 99a represents H or (C 1 -C 3 )alkyl, or R 98 and R 99 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 100 wherein R 100 represents H or (C 1 -C 3 )alkyl;
3.3)
wherein R 101 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.3.a) halogen; and
3.3.b) phenyl;
3.4)
wherein
R 102 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 103 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.4.a) halogen;
3.4.b) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.4.c) phenyl;
3.4.d) —S(O) 2 CH 3 ;
3.4.e) OR 104 wherein R 104 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
3.4.f) —NR 105 R 106 in which R 105 and R 106 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 105 and R 106 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 107 wherein R 107 represents H or (C 1 -C 3 )alkyl;
3.6) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N;
3.7) halogen; or
3.8) —CN;
R 4 represents
4.1) —(C 1 -C 5 )alkyl which is optionally substituted with
4.1.b) -halogen;
4.1.c) —OR 110 wherein R 110 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.c1) halogen; and
4.1.c5) —NR 112 R 113 in which R 112 and R 113 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 112 and R 113 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 114 wherein R 114 represents H or (C 1 -C 3 )alkyl; or
4.1.d) —NR 115 R 116 wherein
R 115 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen and
R 116 represents H, optionally substituted phenyl, or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.d1) halogen;
4.1.d2) —S(O) 2 CH 3 ;
4.1.d3) OR 117 wherein R 117 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.d4) —NR 118 R 119 in which R 118 and R 119 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 118 and R 119 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 120 wherein R 120 represents H or (C 1 -C 3 )alkyl;
4.2)
wherein R 121 represents —(C 1 -C 3 )alkyl which may optionally bear halogen;
d represents 1, 2, or 3;
e represents 0 or 1;
f represents 0, 1, or 2;
4.3)
wherein R 123 represents —(C 1 -C 3 )alkyl which may optionally bear halogen;
g represents 1, 2, or 3;
h represents 0, 1, or 2;
4.4)
wherein
R 125 represents
4.4.a) H;
4.4.b) —(C 1 -C 3 )alkyl which may optionally bear halogen;
4.4.c) —SO 2 R 127 wherein R 127 represents optionally substituted phenyl, or —(C 1 -C 3 )alkyl which may optionally bear halogen;
4.4.d) —C(O)R 129 wherein
R 129 represents
4.4.d1) optionally substituted phenyl,
4.4.d2) —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.4.d2.1) halogen; and
4.4.d2.4) —OR 130 wherein R 130 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.4.d3) —OR 134 wherein R 134 represents (C 1 -C 3 )alkyl; or
4.4.d4) NR 135 R 136 wherein R 135 and R 136 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
j represents 1, 2, or 3;
4.5)
wherein
X represents C or N;
R 138 represents
4.5.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
4.5.a1) halogen;
4.5.a2) OR 139 wherein R 139 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.5.a3) —NR 140 R 141 in which R 140 and R 141 are independently H or —(C 1 -C 3 )alkyl, or R 140 and R 141 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 142 wherein R 142 represents H or (C 1 -C 3 )alkyl;
4.5.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
4.5.b1) halogen;
4.5.c) OR 144 wherein
R 144 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or
(C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
4.5.c1) halogen;
4.5.c2) OR 145 wherein R 145 represents H or (C 1 -C 3 )alkyl; and
4.5.c3) NR 146 R 147 in which R 146 and R 1473 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 146 and R 147 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 148 wherein R 148 represents H or (C 1 C 3 )alkyl;
4.5.e) —C(O)—NR 150 R 151 wherein
R 150 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 151 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.e1) halogen; or
4.5.e6) —NR 153 R 154 in which R 153 and R 154 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 153 and R 154 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 155 wherein R 155 represents H or (C 1 -C 3 )alkyl;
4.5.f) —N(R 156 )—C(O)—R 157 wherein
R 156 represents H or (C 1 -C 3 )alkyl; and
R 157 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl;
4.5.g) —SO 2 NR 162 R 163 wherein
R 162 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 163 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.g1) halogen; or
4.5.g6) —NR 165 R 166 in which R 165 and R 166 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 165 and R 166 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 167 wherein R 167 represents H or (C 1 -C 3 )alkyl;
4.5.h) —N(R 168 )—SO 2 —R 169 wherein
R 168 represents H or (C 1 -C 3 )alkyl, and
R 169 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
4.5.h1) halogen; or
4.5.h4) NR 171 R 172 wherein R 171 and R 172 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 171 and R 172 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 13 wherein R 173 represents H or (C 1 -C 3 )alkyl;
4.5.i) —NR 174 R 175 in which R 174 and R 175 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 175a wherein R 175a represents H or (C 1 -C 3 )alkyl, or R 174 and R 175 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 176 wherein R 176 represents H or (C 1 -C 3 )alkyl;
4.5.j) halogen;
4.5.l) NO 2 ;
4.5.m) CN; or
4.5.n) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan; and
k represents 0, 1, or 2;
4.6)
wherein R 177 represents H or —(C 1 -C 3 )alkyl; and
m represents 1, 2, or 3;
4.7)
wherein
n represents 1, 2, or 3; and
p represents 0, 1, or 2;
4.8)
wherein
q represents 1, 2, or 3;
4.9)
wherein
R 178 represents
4.9.a) H;
4.9.b) —(C 1 -C 3 )alkyl which may optionally bear halogen;
4.9.c) —SO 2 R 180 wherein R 180 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl, which may be substituted with halogen;
4.9.d) —C(O)R 182 wherein R 182 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.9.d1) halogen; and
4.9.d4) OR 183 wherein R 183 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.9e) —C(O)OR 187 wherein R 187 represents (C 1 -C 3 )alkyl; or
4.9.f) —C(O)—NR 188 R 189 wherein R 188 and R 189 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen;
r represents 0, 1, or 2; and
s represents 0 or 1;
4.10)
wherein
R 191 represents
4.10.a) H;
4.10.b) —(C 1 -C 3 )alkyl which may optionally bear halogen;
4.10c) —SO 2 R 193 wherein R 193 represents phenyl or —(C 1 -C 3 )alkyl, both of which may be substituted with halogen;
4.10.d) —C(O)R 194 wherein R 194 represents (C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.10.d1) halogen;
4.10.d2) phenyl; and
4.10.d4) OR 195 wherein R 195 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.10.e) —C(O)OR 199 wherein R 199 represents (C 1 -C 3 )alkyl; or
4.10.f) —C(O)—NR 200 R 201 wherein R 200 and R 201 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen;
X represents O, S, S(O) 2 , or NR 203 wherein
R 203 represents H or —(C 1 -C 3 )alkyl; and
t represents 0, 1, or 2;
4.11) halogen; or
4.12) —CN;
or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 wherein in formula (I)
R 1 represents
1.1) phenyl which may optionally bear up to 4 substituents independently selected from the group consisting of
1.1.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.1.a1) halogen;
1.1.a2) OR 5 wherein R 5 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.1.a3) —NR 6 R 7 in which R 6 and R 7 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or R 6 and R 7 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 8 wherein R 8 represents H or (C 1 -C 3 )alkyl; and
1.1.a4) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
1.1.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.1.b1) halogen;
1.1.c) OR 10 wherein
R 10 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.1.c1) halogen;
1.1.c2) OR 11 wherein R 11 represents H or (C 1 -C 3 )alkyl; and
1.1.c3) NR 12 R 13 in which R 12 and R 13 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 12 and R 13 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 14 wherein R 14 represents H or (C 1 -C 3 )alkyl;
1.1.e) —C(O)—NR 16 R 17 wherein
R 16 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 17 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.1.e1) halogen;
1.1.e5) —OR 18 wherein R 18 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.e6) —NR 19 R 20 in which R 19 and R 20 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 19 and R 20 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 21 wherein R 21 represents H or (C 1 -C 3 )alkyl;
1.1.f) —N(R 22 )—C(O)—R 23 wherein
R 22 represents H or (C 1 -C 3 )alkyl; and
R 23 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl;
1.1.g) —SO 2 NR 28 R 29 wherein
R 28 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 29 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with:
1.1.g1) halogen;
1.1.g4) —SO 2 CH 3 ;
1.1.g5) —OR 30 wherein R 30 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
1.1.g6) —NR 31 R 32 in which R 31 and R 32 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 31 and R 32 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 33 wherein R 33 represents H or (C 1 -C 3 )alkyl;
1.1.h) —N(R 34 )—SO 2 —R 35 wherein
R 34 represents H or (C 1 -C 3 )alkyl, and
R 35 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.1.h1) halogen;
1.1.i) —NR 40 R 41 in which R 40 and R 41 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 42 in which R 42 represents H or (C 1 -C 3 )alkyl, or R 40 and R 41 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 43 wherein R 43 represents H or (C 1 -C 3 )alkyl;
1.1.j) halogen;
1.1.l) NO 2 ;
1.1.m) CN; and
1.1.n) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
or
R 1 represents
1.2) a 5-6 membered aromatic heterocycle selected from imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, and furan; said R 1 heterocycle optionally bearing up to 4 substituents independently selected from the group consisting of
1.2.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.2.a1) halogen;
1.2.a2) OR 45 wherein R 45 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.a3) —NR 46 R 47 in which R 46 and R 47 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 46 and R 47 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 48 wherein R 48 represents H or (C 1 -C 3 )alkyl; and
1.2.a4) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
1.2.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.2.b1) halogen;
1.2.c) OR 50 wherein
R 50 represents H; phenyl; benzyl; —(C 3 -C 6 )cycloalkyl; or —(C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.2.c1) halogen;
1.2.e) —C(O)—NR 56 R 57 wherein
R 56 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 57 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.e1) halogen; or
1.2.e5) —OR 58 wherein R 58 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.f) —N(R 62 )—C(O)—R 63 wherein
R 62 represents H or (C 1 -C 3 )alkyl; and
R 63 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl;
1.2.g) —SO 2 NR 68 R 69 wherein
R 68 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 69 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
1.2.g1) halogen; or
1.2.g5) —OR 70 wherein R 70 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.h) —N(R 74 )—SO 2 —R 75 wherein
R 74 represents H or (C 1 -C 3 )alkyl, and
R 75 represents optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
1.2.h1) halogen;
1.2.i) —NR 80 R 81 in which R 80 and R 81 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 81a wherein R 81a represents H or (C 1 -C 3 )alkyl, or R 80 and R 81 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 82 wherein R 82 represents H or (C 1 -C 3 )alkyl;
1.2.j) halogen;
1.2.k) optionally substituted phenyl;
1.2.l) NO 2 ;
1.2.m) CN; and
1.2.n) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
R 2 represents hydrogen; halogen; —(C 1 -C 5 )alkyl which may optionally bear halogen; or —O(C 1 -C 3 )alkyl which may optionally bear halogen;
R 3 represents
3.1) —(C 1 -C 5 )alkyl which is substituted with
3.1.a) -halogen;
3.1.c) a 5-6 membered heteroaromatic containing up to two heteroatoms selected from O, S, and N, optionally substituted with halogen or —(C 1 -C 3 )alkyl,
3.1.d) —CN,
3.1.e) —OR 83 wherein R 83 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
3.1.e1) halogen; and
3.1.e4) OR 84 wherein R 84 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
3.1.f) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.1.g) —NR 89 R 90 wherein
R 89 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 90 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
3.1.g1) halogen;
3.1.g4) —SO 2 CH 3 ;
3.1.g5) —OR 91 wherein R 91 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; or
3.1.g7) R 89 and R 90 may be joined and taken together with the N to which they are attached form an aromatic or nonaromatic 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 95 wherein R 95 represents H or (C 1 -C 3 )alkyl;
3.2)
wherein
R 96 represents
3.2.b) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.2.c) —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.2.c1) halogen; and
3.2.c5) —OR 97 wherein R 97 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
3.3)
wherein R 101 represents H or —(C 1 -C 5 )alkyl;
3.4)
wherein
R 102 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 103 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.4.a) halogen;
3.4.d) —S(O) 2 CH 3 ; and
3.4.e) OR 104 wherein R 104 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
3.6) a 5-6 membered aromatic heterocycle selected from imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, and furan;
3.7) halogen; or
3.8) —CN;
R 4 represents
4.1) —(C 1 -C 5 )alkyl which is substituted with
4.1.b) -halogen;
4.1.c) —OR 110 wherein R 110 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.c1) halogen; and
4.1.c5) —NR 112 R 113 in which R 112 and R 113 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 112 and R 113 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 114 wherein R 114 represents H or (C 1 -C 3 )alkyl; or
4.1.d) —NR 115 R 116 wherein
R 115 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen and
R 116 represents H, optionally substituted phenyl, or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.d1) halogen;
4.1.d2) —S(O) 2 CH 3 ;
4.1.d3) OR 117 wherein R 117 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.d4) —NR 118 R 119 in which R 118 and R 119 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 118 and R 119 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 120 wherein R 120 represents H or (C 1 -C 3 )alkyl;
4.2)
wherein R 121 represents —(C 1 -C 3 )alkyl which may optionally bear halogen;
d represents 1, 2, or 3;
e represents 0 or 1;
f represents 0, 1, or 2;
4.3)
wherein R 123 represents —(C 1 -C 3 )alkyl which may optionally bear halogen;
g represents 1, 2, or 3;
h represents 0, 1, or 2;
4.4)
wherein
R 125 represents
4.4.a) H;
4.4.b) —(C 1 -C 3 )alkyl which may optionally bear halogen;
4.4.c) —SO 2 R 127 wherein R 127 represents optionally substituted phenyl, or —(C 1 -C 3 )alkyl which may optionally bear halogen;
4.4.d) —C(O)R 129 wherein
R 129 represents
4.4.d1) optionally substituted phenyl,
4.4.d2) —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.4.d2.1) halogen; and
4.4.d2.4) —OR 130 wherein R 130 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.4.d3) —OR 134 wherein R 134 represents (C 1 -C 3 )alkyl; or
4.4.d4) NR 135 R 136 wherein R 135 and R 136 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
j represents 1, 2, or 3;
4.5)
wherein
X represents C or N;
R 138 represents
4.5.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
4.5.a1) halogen;
4.5.a2) OR 139 wherein R 139 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.5.a3) —NR 140 R 141 in which R 140 and R 141 are independently H or —(C 1 -C 3 )alkyl, or R 140 and R 141 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 142 wherein R 142 represents H or (C 1 -C 3 )alkyl;
4.5.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
4.5.b1) halogen;
4.5.c) OR 144 wherein
R 144 represents H; phenyl; benzyl; (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
4.5.c1) halogen;
4.5.c2) OR 145 wherein R 145 represents H or (C 1 -C 3 )alkyl; and
4.5.c3) NR 146 R 147 in which R 146 and R 1473 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 146 and R 147 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 148 wherein R 148 represents H or (C 1 -C 3 )alkyl;
4.5.e) —C(O)—NR 150 R 151 wherein
R 150 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 151 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.e1) halogen; or
4.5.e6) —NR 153 R 154 in which R 153 and R 154 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 153 and R 154 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 155 wherein R 155 represents H or (C 1 -C 3 )alkyl;
4.5.f) —N(R 156 )—C(O)—R 157 wherein
R 156 represents H or (C 1 -C 3 )alkyl; and
R 157 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl;
4.5.g) —SO 2 NR 162 R 163 wherein
R 162 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
R 163 represents H or —(C 1 -C 4 )alkyl which is optionally substituted with
4.5.g1) halogen; or
4.5.g6) —NR 165 R 166 in which R 165 and R 166 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 165 and R 166 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 167 wherein R 167 represents H or (C 1 -C 3 )alkyl;
4.5.h) —N(R 168 )—SO 2 -—R 169 wherein
R 168 represents H or (C 1 -C 3 )alkyl, and
R 169 represents H, optionally substituted phenyl, or (C 1 -C 4 )alkyl which is optionally substituted with
4.5.h1) halogen; or
4.5.h4) NR 171 R 172 wherein R 171 and R 172 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 171 and R 172 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 173 wherein R 173 represents H or (C 1 -C 3 )alkyl;
4.5.i) —NR 174 R 175 in which R 174 and R 175 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen or OR 175a wherein R 175a represents H or (C 1 -C 3 )alkyl, or R 174 and R 175 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 176 wherein R 176 represents H or (C 1 -C 3 )alkyl;
4.5.j) halogen;
4.5.l) NO 2 ;
4.5.m) CN; or
4.5.n) a 5-6 membered aromatic heterocycle selected from imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, and furan; and
k represents 0, 1, or 2;
4.6)
wherein R 177 represents H or —(C 1 -C 3 )alkyl; and
m represents 1, 2, or 3;
4.7)
wherein
n represents 1, 2, or 3; and
p represents 0, 1, or 2;
4.8)
wherein
q represents 1, 2, or 3;
4.9)
wherein
R 178 represents
4.9.a) H;
4.9.b) —(C 1 -C 3 )alkyl which may optionally bear halogen;
4.9.c) —SO 2 R 180 wherein R 180 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl, which may be substituted with halogen;
4.9.d) —C(O)R 182 wherein R 182 represents optionally substituted phenyl or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.9.d1) halogen; and
4.9.d4) OR 183 wherein R 183 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.9e) —C(O)OR 187 wherein R 187 represents (C 1 -C 3 )alkyl; or
4.9.f) —C(O)—NR 188 R 189 wherein R 188 and R 189 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen;
r represents 0, 1, or 2; and
s represents 0 or 1;
4.10)
wherein
R 191 represents
4.10.a) H;
4.10.b) —(C 1 -C 3 )alkyl which may optionally bear halogen;
4.10c) —SO 2 R 193 wherein R 193 represents phenyl or —(C 1 -C 3 )alkyl, both of which may be substituted with halogen;
4.10.d) —C(O)R 194 wherein R 194 represents (C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.10.d1) halogen;
4.10.d2) phenyl; and
4.10.d4) OR 195 wherein R 195 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen;
4.10.e) —C(O)OR 199 wherein R 199 represents (C 1 -C 3 )alkyl; or
4.10.f) —C(O)_NR 200 R 201 wherein R 200 and R 201 each independently represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen;
X represents O, S, S(O) 2 , or NR 203 wherein
R 203 represents H or —(C 1 -C 3 )alkyl; and
t represents 0, 1, or 2;
4.11) halogen; or
4.12) —CN;
or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 wherein in formula (I)
R 1 represents
1.1) phenyl which may optionally bear up to 4 substituents independently selected from the group consisting of
1.1.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.1.a1) halogen;
1.1.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.1.b1) halogen;
1.1.c) OR 10 wherein
R 10 represents H, or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.1.c1) halogen;
1.1.i) —NR 40 R 41 in which R 40 and R 41 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen;
1.1.j) halogen;
1.1.l) NO 2 ; and
1.1.m) CN;
or
R 1 represents
1.2) a 5-6 membered aromatic heterocycle selected from thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, and thiophene; said R 1 heterocycle optionally bearing up to 4 substituents independently selected from the group consisting of
1.2.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
1.2.a1) halogen; and
1.2.a4) an imidazole, thiazole, oxazole, pyridine, pyrazole, pyrimidine, isoxazole, isothiazole, thiophene, or furan;
1.2.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
1.2.b1) halogen;
1.2.c) OR 50 wherein
R 50 represents —(C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
1.2.c1) halogen;
1.2.i) —NR 80 R 81 in which R 80 and R 81 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen;
1.2.j) halogen;
1.2.k) optionally substituted phenyl;
1.2.l) NO 2 ; and
1.2.m) CN;
R 2 represents hydrogen; halogen or —(C 1 -C 5 )alkyl;
R 3 represents
3.1) —(C 1 -C 5 )alkyl which is substituted with
3.1.a) -halogen;
3.1.d) —CN; or
3.1.e) —OR 83 wherein R 83 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
3.1.e1) halogen;
3.1.g) —NR 89 R 90 wherein
R 89 represents H; and
R 90 represents —(C 1 -C 4 )alkyl which is optionally substituted with —OR 91 wherein R 91 represents H or (C 1 -C 3 )alkyl;
3.2)
wherein
R 96 represents
3.2.b) —(C 3 -C 5 )cycloalkyl which may optionally bear halogen; or
3.2.c) —(C 1 -C 5 )alkyl;
3.3)
wherein R 101 represents H or —(C 1 -C 5 )alkyl;
3.4)
wherein
R 102 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen; and
R 103 represents H or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
3.4.a) halogen;
3.6) a 5-6 membered aromatic heterocycle selected from imidazole, thiazole, oxazole, pyrazole, isoxazole, and isothiazole;
3.7) halogen; or
3.8) —CN;
R 4 represents
4.1) —(C 1 -C 5 )alkyl which is substituted with
4.1.b) -halogen;
4.1.c) —OR 110 wherein R 110 represents H or —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.c1) halogen; or
4.1.d) —NR 115 R 116 wherein
R 115 represents H or —(C 1 -C 3 )alkyl which may optionally bear halogen, and
R 116 represents H, optionally substituted phenyl, or —(C 1 -C 5 )alkyl which may optionally bear up to 3 substituents independently selected from
4.1.d1) halogen;
4.1.d3) OR 117 wherein R 117 represents H or (C 1 -C 3 )alkyl which may optionally bear halogen; and
4.1.d4) —NR 118 R 119 in which R 118 and R 119 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen, or R 118 and R 119 may be joined and taken together with the N atom to which they are attached form a 5-6 membered ring which may optionally contain a ring member selected from O, S, and NR 120 wherein R 120 represents H or (C 1 -C 3 )alkyl;
4.2)
wherein R 121 represents —(C 1 -C 3 )alkyl which may optionally bear halogen;
d represents 1, 2, or 3;
e represents 0 or 1;
f represents 0, 1, or 2;
4.3)
wherein R 123 represents —(C 1 -C 3 )alkyl which may optionally bear halogen;
g represents 1, 2, or 3;
h represents 0, 1, or 2;
4.4)
wherein
R 125 represents
4.4.a) H;
4.4.b) —(C 1 -C 3 )alkyl;
4.4.c) —SO 2 R 127 wherein R 127 represents optionally substituted phenyl, or —(C 1 -C 3 )alkyl;
4.4.d) —C(O)R 129 wherein
R 129 represents
4.4.d2) —(C 1 -C 3 )alkyl which may optionally bear
4.4.d2.4) —OR 130 wherein R 130 represents H or (C 1 -C 3 )alkyl;
4.4.d3) —OR 134 wherein R 134 represents (C 1 -C 3 )alkyl; or
4.4.d4) NR 135 R 136 wherein R 135 and R 136 are independently H or —(C 1 -C 3 ); and
j represents 1, 2, or 3;
4.5)
wherein
X represents C or N;
R 138 represents
4.5.a) (C 1 -C 4 )alkyl, which may optionally bear up to 3 substituents independently selected from
4.5.a1) halogen;
4.5.b) —(C 3 -C 6 )cycloalkyl which may optionally bear up to 2 substituents independently selected from
4.5.b1) halogen;
4.5.c) OR 144 wherein
R 144 represents H, or (C 1 -C 4 )alkyl which may optionally bear up to 3 substituents independently selected from
4.5.c1) halogen;
4.5.i) —NR 174 R 175 in which R 174 and R 175 are independently H or —(C 1 -C 3 )alkyl which may optionally bear halogen;
4.5.j) halogen;
4.5.l) NO 2 ; or
4.5.m) CN; and
k represents 0, 1, or 2;
4.6)
wherein
R 177 represents H or —(C 1 -C 3 )alkyl; and
m represents 1, 2, or 3;
4.7)
wherein
n represents 1, 2, or 3; and
p represents 0, 1, or 2;
4.8)
wherein
q represents 1, 2, or 3;
4.9)
wherein
R 178 represents
4.9.a) H;
4.9.b) —(C 1 -C 3 )alkyl;
4.9.c) —SO 2 R 180 wherein R 180 represents —(C 1 -C 3 )alkyl;
4.9.d) —C(O)R 182 wherein R 182 represents —(C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.9.d4) OR 183 wherein R 183 represents H or (C 1 -C 3 )alkyl;
4.9e) —C(O)OR 187 wherein R 187 represents (C 1 -C 3 )alkyl; or
4.9.f) —C(O)—NR 188 R 189 wherein R 188 and R 189 each independently represents H or —(C 1 -C 3 )alkyl;
r represents 0, 1, or 2; and
s represents 0 or 1;
4.10)
wherein
R 191 represents
4.10.a) H;
4.10.b) —(C 1 -C 3 )alkyl;
4.10c) —SO 2 R 193 wherein R 193 represents —(C 1 -C 3 )alkyl;
4.10.d) —C(O)R 194 wherein R 194 represents (C 1 -C 3 )alkyl which may optionally bear up to 3 substituents independently selected from
4.10.d4) OR 195 wherein R 195 represents H or (C 1 -C 3 )alkyl;
4.10.e) —C(O)OR 199 wherein R 199 represents (C 1 -C 3 )alkyl; or
4.10.f) —C(O)—NR 200 R 201 wherein R 200 and R 201 each independently represents H or —(C 1 -C 3 )alkyl;
X represents O, S, S(O) 2 , or NR 203 wherein
R 203 represents H or —(C 1 -C 3 )alkyl; and
t represents 0, 1, or 2;
4.11) halogen; or
4.12) —CN;
or a pharmaceutically acceptable salt thereof.
8. A compound of formula (Q1)
wherein
R represents H or (C 1 -C 5 )alkyl; and
R 2 represents halogen; —(C 1 -C 5 )alkyl which may optionally bear halogen; or —O(C 1 -C 3 )alkyl which may optionally bear halogen.
9. A compound of formula
wherein
G 3 represents halogen, (C 1 -C 5 )alkyl, —CN, —C(O)O(C 1 -C 5 )alkyl, or —C(O)H.
10. A compound selected from the following list:
4-amino-5-{4-[({[2-fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)-amino]-phenyl}-7-(morpholin-4-ylmethyl)-N-(2,2,2-trifluoroethyl)-pyrrolo[2,1-f][1,2,4]-triazine-6-carboxamide;
4-amino-5-{4-[({[2-fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)-amino]phenyl}-7-[(4-methylpiperazin-1-yl)methyl]-N-(2,2,2-trifluoroethyl)-pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;
N-{4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)-pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-(4-[4-amino-6-(methoxymethyl)-7-[(4-methylpiperazin-1-yl)methyl]-pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl)-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-{4-[4-amino-7-{[(2-methoxyethyl)amino]methyl}-6-(methoxymethyl)-pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-{4-[4-amino-7-[(2,6-dimethylmorpholin-4-yl)methyl]-6-(methoxymethyl)-pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-(4-[4-amino-6-(methoxymethyl)-7-[(3-oxopiperazin-1-yl)methyl]-pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl)-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-{4-[4-amino-7-{[(2-methoxyethyl)(methyl)amino]methyl}-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-7-(morpholin-4-ylmethyl)-6-(1,3-oxazol-5-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-7-(morpholin-4-ylmethyl)-6-(1,3-oxazol-5-yl)-pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-{4-[4-amino-7-{[(2R,6S)-2,6-dimethylmorpholin-4-yl]methyl}-6-(1,3-oxazol-5-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-7-[(4-methylpiperazin-1-yl)methyl]-6-(1,3-oxazol-5-yl)-pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-{4-[4-amino-7-(morpholin-4-ylmethyl)-6-(1,3-oxazol-5-yl)-pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-{4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)-pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-(4-[4-amino-6-(methoxymethyl)-7-[(3-oxopiperazin-1-yl)methyl]-pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl)-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-(4-[4-amino-6-(methoxymethyl)-7-[(3-oxopiperazin-1-yl)methyl]-pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl)-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
rel-N-{4-[4-amino-7-{[(2R,6S)-2,6-dimethylmorpholin-4-yl]methyl}-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)-pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-chloro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-7-(morpholin-4-ylmethyl)-6-(1,3-oxazol-5-yl)-pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-{4-[6-acetyl-4-amino-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f]-[1,2,4]-triazin-5-yl]-2-fluorophenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[6-acetyl-4-amino-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]-2-fluorophenyl}-N′-[3-(trifluoromethyl)phenyl]urea;
N-{4-[6-acetyl-4-amino-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]-2-fluorophenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-{4-[4-amino-6-(cyanomethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-{4-[4-amino-6-(cyanomethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-(cyanomethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-{4-[4-amino-6-(difluoromethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-{4-[4-amino-6-(cyclopropylcarbonyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-{4-[4-amino-6-(difluoromethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-{4-[6-acetyl-4-amino-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]-2-fluorophenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-(difluoromethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-{4-[4-amino-6-methyl-7-(1,4-oxazepan-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-{4-[4-amino-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]phenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
1-{4-[4-amino-6-methyl-7-(1,4-oxazepan-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]-2-fluorophenyl}-3-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-{4-[4-amino-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]-2-fluorophenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
1-{4-[4-amino-6-(methoxymethyl)-7-(1,4-oxazepan-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-{4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-(2-fluoro-5-methylphenyl)urea;
N-{4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[3-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-(4-tert-butylpyridin-2-yl]urea;
N-{4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-{4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-(3-tert-butylphenyl)urea;
N-{4-[4-amino-6-(methoxymethyl)-7-(1,4-oxazepan-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-N′-[3-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2,5-difluorophenyl}-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
N-[4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-methylphenyl]-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea;
1-{4-[4-amino-7-{[(2-hydroxyethyl)amino]methyl}-6-(methoxymethyl)-pyrrolo[2,1-f][1,2,4]triazin-5-yl}-2-fluorophenyl)-3-[2-fluoro-5-(trifluoro-methyl)phenyl]urea;
1-(4-{4-amino-6-(methoxymethyl)-7-[(3-methylmorpholin-4-yl)methyl]-pyrrolo[2,1-f][1,2,4]triazin-5-yl}-2-fluorophenyl)-3-[2-fluoro-5-(trifluoro-methyl)phenyl]urea;
N-{4-[4-amino-6-chloro-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]-2-fluorophenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-chloro-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-chloro-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]-2-fluorophenyl}-N′-[3-(trifluoromethyl)phenyl]urea;
N-{4-[4-amino-6-chloro-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]-2-fluorophenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea;
N-{4-[4-amino-6-chloro-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]-2-fluorophenyl}-N′-(2-fluoro-5-methylphenyl)urea.
11. A pharmaceutical composition comprising a compound as defined in claim 1 , plus a pharmaceutically acceptable carrier.
12. A method of treating breast cancer in a mammal, comprising
administering to said mammal an effective amount of a compound as defined in claim 1 .
13. The method of claim 12 wherein said mammal is a human.Cited by (0)
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